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Polymerase Chain Reaction Detection of DNA Sequence Deletions

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Allelic loss of human chromosome sequences contributes to tumorigenesis through the inactivation of putative tumor-suppressor genes. The Knudson hypothesis proposes that deletion or mutation must affect both alleles of the gene in order to disable tumor suppression (1 ). As might be expected, the effect of “two hits” on tumor-suppressor gene integrity—e.g., deletion of one allele and mutation of the remaining allele—would disable the gene from encoding gene product. The von Hippel-Lindau (VHL) gene is an example of a tumorsuppressor gene that fulfills the Knudson hypothesis—e.g., one mutant allele is inherited in the germline, and the other is mutated or deleted somatically in many clear-cell renal cell carcinomas (recently reviewed in ref. 2 ).
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